Phenylketonuria (PKU) causes mental retardation in children. The underlying cause of PKU is not well understood. The critical biochemical parameters and reaction in the development of PKU is plasma phenylalanine elevation whereas tyrosine is maintained at a relatively low level. The serotonergic system has consistently been implicated in the pathogenesis of PKU. The goal of this research is to determine if changes in serotonin receptors (5-HT2C) contribute to the conditions associated with PKU by inducing the primary characteristics of PKU beginnings in 9-day-old rats. To achieve this goal, animal models of PKU will be used to examine a number of pharmacological parameters, including quantitation of serotonin levels by means of high performance liquid chromatography (HPLC), and radioligand binding assays that are coupled with determinations of blood phenylalanine levels. The findings of this work may contribute toward an understanding of the mechanisms involved in this disease.